Article
Cell Biology
Rebecca A. Mosig, Allison N. Castaneda, Jacob C. Deslauriers, Landon P. Frazier, Kevin L. He, Naseem Maghzian, Aarati Pokharel, Camille T. Schrier, Lily Zhu, Nobuya Koike, John J. Tyson, Carla B. Green, Joseph S. Takahashi, Shihoko Kojima
Summary: In mammals, the Per2AS transcript inhibits Per2 expression in a double negative feedback loop, maintaining Per2 levels within the oscillatory range. This regulation is important for the circadian clock machinery and cannot be solely explained by Per2 interaction.
GENES & DEVELOPMENT
(2021)
Article
Medicine, Research & Experimental
Yijing Zhao, Lei Zhou, Hui Li, Tingge Sun, Xue Wen, Xueli Li, Ying Meng, Yan Li, Mengmeng Liu, Shanshan Liu, Su-Jeong Kim, Jialin Xiao, Lingyu Li, Songling Zhang, Wei Li, Pinchas Cohen, Andrew R. Hoffman, Ji-Fan Hu, Jiuwei Cui
Summary: The study revealed that in hepatoma cells, the lncRNA MALAT1 interacts with various loci on mitochondrial DNA, leading to abnormalities in mitochondrial function and subsequently impacting tumor phenotype and pathways related to cellular mitochondria. The findings suggest a critical role of MALAT1 in regulating mitochondrial metabolism and tumor metabolism reprogramming.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2021)
Article
Cell Biology
Ghulam Mohammad, Renu A. Kowluru
Summary: Diabetes damages retinal mitochondria, leading to degenerative capillaries. Long noncoding RNAs like LncMALAT1 and LncNEAT1 play a crucial role in this process, influencing mitochondrial homeostasis and protecting mitochondrial structural and genomic integrity.
Article
Biology
Zhenxing Song, Ruirui Jia, Mingfeng Tang, Fei Xia, Haiyang Xu, Zhengguo Li, Chuan Huang
Summary: Antisense oligonucleotides (ASOs) are powerful molecular tools widely used in protein and RNA biology, and are highly selective therapeutic strategies for many diseases. Research shows that linear RNA ASO can attenuate transcription of nascent transcripts by inducing premature transcription termination, while circRNA ASO transfection does not affect transcription activity of the encoded gene.
SCIENCE CHINA-LIFE SCIENCES
(2021)
Review
Virology
Rui Li, Rachel Sklutuis, Jennifer L. Groebner, Fabio Romerio
Summary: Natural antisense transcripts (NATs) are RNA molecules transcribed from the opposite strand of a protein-coding gene, with the ability to regulate the expression of the gene. HIV-1 produces NATs from a promoter within the 3' long terminal repeat, but the complete role of these transcripts in the virus lifecycle remains unclear despite over 30 years of research.
Article
Oncology
Haihua Tian, Jinchang Pan, Shuai Fang, Chengwei Zhou, Hui Tian, Jinxian He, Weiyu Shen, Xiaodan Meng, Xiaofeng Jin, Zhaohui Gong
Summary: The upregulation of the antisense lncRNA DPP10-AS1 promotes malignant processes in lung cancer by regulating its sense gene DPP10 epigenetically. DPP10-AS1 could potentially serve as a candidate prognostic biomarker and a therapeutic target in lung cancer due to its effects on tumor growth and apoptosis suppression.
CANCER BIOLOGY & MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Binyuan Jiang, Yeqin Yuan, Ting Yi, Wei Dang
Summary: Antisense long noncoding RNA (as-lncRNA) is a reverse transcription product that is partially or completely complementary to the corresponding sense protein-coding or noncoding genes. As-lncRNAs, also known as natural antisense transcripts (NATs), can regulate the expression of adjacent sense genes through various mechanisms, influencing cellular activities and participating in the development of various tumors. This study aims to explore the functional roles of as-lncRNAs in cis-regulating protein-coding sense genes and provide a theoretical basis for lncRNA-targeted tumor therapy by comprehensively understanding the occurrence and development of malignant tumors.
Article
Biochemistry & Molecular Biology
Xiangmou Qin, Shuangshuang Feng, Yanwei Zhang, Jianguo Su, Li Lin, Yong-an Zhang, Jiagang Tu
Summary: The study identified two groups of SHVV leader RNAs and revealed that one of the groups, le(group1), affects SHVV replication by interacting with the viral nucleoprotein (N). The critical region for this interaction was identified as nucleotides 6-10 of le(group1) and amino acids 1-45 of the N protein. This research provides insights into the role of leader RNA in regulating the replication of negative-stranded RNA viruses.
Article
Biochemistry & Molecular Biology
Fei Wang, Qianqian Wang, Baowei Liu, Lisheng Mei, Sisi Ma, Shujuan Wang, Ruoyu Wang, Yan Zhang, Chaoshi Niu, Zhiqi Xiong, Yong Zheng, Zhi Zhang, Juan Shi, Xiaoyuan Song
Summary: The highly expressed lncRNA Synage in the cerebellum regulates synaptic stability through multiple mechanisms, including serving as a sponge for microRNA miR-325-3p and as a scaffold for organizing protein complexes in synapses. Deletion of Synage leads to a spectrum of cerebellar abnormalities in mice, ultimately resulting in motor dysfunction in adults.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Biochemistry & Molecular Biology
Makoto Arai, Hiroki Ochi, Satoko Sunamura, Nobuaki Ito, Masaomi Nangaku, Shu Takeda, Shingo Sato
Summary: This study identified a novel osteocyte-specific long noncoding RNA (lncRNA953Rik) that suppresses osteogenic differentiation by inhibiting the Wnt/beta-catenin signaling pathway. This research clarifies the role of lncRNAs in osteocytes for the first time and provides new therapeutic options for bone metabolic diseases such as osteoporosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Yingmin Zhang, Xinhua Qiao, Lihui Liu, Wensheng Han, Qinghua Liu, Yuanyuan Wang, Ting Xie, Yiheng Tang, Tiepeng Wang, Jiao Meng, Aojun Ye, Shunmin He, Runsheng Chen, Chang Chen
Summary: The downregulation of MAGI2-AS3 decreases superoxide levels and hydrogen peroxide content by stabilizing the HSPA8 protein level, leading to delayed cell senescence through the suppression of the ROS/MAP2K6/p38 signaling pathway. These findings suggest a potential anti-aging application.
Article
Biochemistry & Molecular Biology
Gabriele Floris, Aria Gillespie, Mary Tresa Zanda, Konrad R. Dabrowski, Stephanie E. Sillivan
Summary: The number of opioid overdose deaths continues to rise in the United States, making it crucial to understand the neurobiological adaptations caused by chronic heroin exposure. This study explores the regulation of circular RNAs (circRNAs) by heroin in the rat orbitofrontal cortex (OFC), a brain region involved in rewarding stimuli. The findings suggest that heroin regulates the expression of specific circRNAs in the OFC, which could impact cellular processes related to opioid addiction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Fisheries
Yanhong Song, Weiwei Zheng, Shiying Xin, Jiajia Pan, Liyuan Yang, Yuena Sun, Tianjun Xu
Summary: This study identified a novel long noncoding RNA (lncRNA) called LTCONS6801 in Miichthys miiuy, which contributes to the TANK-binding kinase 1 (TBK1) pathway and promotes the host immune function. The overexpression of lncRNA LTCONS6801 was found to enhance cell activity and increase the expression of antiviral genes and TBK1. Furthermore, lncRNA LTCONS6801 was found to regulate the NF-kappa B and IRF3 signaling pathways by modulating TBK1 expression. In conclusion, lncRNA LTCONS6801 positively regulates the host innate immune response by controlling TBK1 expression, highlighting its important role in antiviral immunity of teleost fish.
FISH & SHELLFISH IMMUNOLOGY
(2023)
Review
Cell Biology
Carlos Gorbea, Abdalla Elhakiem, Demian Cazalla
Summary: Just like host cells, viruses also express different classes of noncoding RNAs (ncRNAs) to control the cellular environment. These viral ncRNAs have diverse functions, including regulating viral replication, latency/reactivation decision, immune evasion, and cellular transformation. Studying the ncRNAs expressed by adenoviruses and herpesviruses has provided insights into RNA-based mechanisms in host cells.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2023)
Article
Immunology
Jingui Deng, Qing Wang, Jing Zhang, Yanping Ma, Ying Qi, Zhongyang Liu, Yibo Li, Qiang Ruan, Yujing Huang
Summary: HCMV-encoded circRNAs are abundantly expressed during HCMV infection. A total of 629 HCMV-encoded circRNAs were identified using RNA deep sequencing. The study verified the existence and transcription of circUS12, circUL55, and circUL89, and revealed the potential roles of HCMV-encoded circRNAs in HCMV infection.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Immunology
Ashley I. Heinson, Jeongmin Woo, Amey Mukim, Cory H. White, Bastiaan Moesker, Alberto Bosque, Celsa A. Spina, Christopher H. Woelk, Ben D. Macarthur, Nadejda Beliakova-Bethell
Summary: Despite significant progress in identifying cellular factors and pathways contributing to the latent HIV reservoir, the major obstacle to eradicating the virus remains. Noncoding genes, including microRNAs, have been implicated in regulating HIV expression during latency. This study revealed dysregulation of miRNAs in a primary CD4(+) T cell model of HIV latency, with a subset targeting pathways relevant to HIV expression and establishment of latency, such as the p53 signaling pathway.
AIDS RESEARCH AND HUMAN RETROVIRUSES
(2021)
Article
Virology
Indra Sarabia, Szu-Han Huang, Adam R. Ward, R. Brad Jones, Alberto Bosque
Summary: The establishment of HIV-1 latency has posed challenges for curing HIV-1. Current strategies to shock and kill the virus reservoir are not effective in inducing the majority of intact HIV-1 proviruses. The mechanisms behind the non-inducible HIV-1 reservoir still need further investigation.
JOURNAL OF VIROLOGY
(2021)
Article
Microbiology
Stuart R. Jefferys, Samuel D. Burgos, Jackson J. Peterson, Sara R. Selitsky, Anne-Marie Turner, Lindsey I. James, Yi-Hsuan Tsai, Alisha R. Coffey, David M. Margolis, Joel Parker, Edward P. Browne
Summary: HIV latency in CD4 T cells is a major barrier to curing HIV infection, characterized by elevated activity of specific transcription factors like Forkhead TFs and Kruppel-like factors, as well as the involvement of the protein CTCF in establishing latency. Targeting these factors may lead to new strategies to eliminate the HIV reservoir.
Article
Pharmacology & Pharmacy
E. A. Innis, C. Levinger, M. A. Szaniawski, E. S. C. P. Williams, J. Alcami, A. Bosque, J. T. Schiffer, M. Coiras, A. M. Spivak, V Planelles
Summary: This study investigated FDA-approved oncology drugs and found that dasatinib, ponatinib, and trametinib can significantly reduce proliferation of memory CD4 T cells in HIV-infected individuals. Dasatinib, in particular, blocks both homeostatic and antigen-driven proliferation and aids in reducing the reservoir size. By inhibiting STAT5 phosphorylation, dasatinib hinders IL-7 induced proliferation and prevents spontaneous rebound in cells from people living with HIV-1.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Callie Levinger, J. Natalie Howard, Jie Cheng, Pingtao Tang, Amit Joshi, Marta Catalfamo, Alberto Bosque
Summary: The assessment of HIV-1 persistence is challenging, with most commercially available tests focusing on the measurement of nucleic acid. Despite their high sensitivity, these assays have limitations in evaluating translational competent viral reservoirs.
SCIENTIFIC REPORTS
(2021)
Correction
Multidisciplinary Sciences
Callie Levinger, J. Natalie Howard, Jie Cheng, Pingtao Tang, Amit Joshi, Marta Catalfamo, Alberto Bosque
SCIENTIFIC REPORTS
(2021)
Article
Education, Scientific Disciplines
Courtney B. Hilton, Micah B. Goldwater, Dale Hancock, Matthew Clemson, Alice Huang, Gareth Denyer
Summary: A critical goal of science education is to design and implement scalable learning activities that foster deep conceptual understanding in students. This study presents a novel design that combines online question authoring with supporting activities to enhance cognitive engagement.
CBE-LIFE SCIENCES EDUCATION
(2022)
Article
Virology
Rachel S. Resop, Alberto Bosque
Summary: Inhibition of SPHK can reduce HIV-1 transmission between CD4 T cells and decrease susceptibility to infection, which may serve as a basis for developing strategies to prevent HIV-1 infection.
JOURNAL OF VIROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Samuel W. Olson, Anne-Marie W. Turner, J. Winston Arney, Irfana Saleem, Chase A. Weidmann, David M. Margolis, Kevin M. Weeks, Anthony M. Mustoe
Summary: This study used a single-molecule chemical probing strategy, DANCE-MaP, to define the structural dynamics of 7SK RNA and revealed its role in regulating transcription and responding to cellular signals.
Article
Virology
Amanda B. Macedo, Callie Levinger, Bryan N. Nguyen, Jonathan Richard, Mamta Gupta, Conrad Russell Y. Cruz, Andres Finzi, Katherine B. Chiappinelli, Keith A. Crandall, Alberto Bosque
Summary: In this study, we found that HODHBt enhances IL-15 signaling in natural killer cells, leading to increased cytotoxicity and memory-like functions. This suggests that pharmacological enhancement of IL-15-mediated STAT activation could be a new approach for HIV treatment.
JOURNAL OF VIROLOGY
(2022)
Article
Multidisciplinary Sciences
Eva M. Stevenson, Sandra Terry, Dennis Copertino, Louise Leyre, Ali Danesh, Jared Weiler, Adam R. Ward, Pragya Khadka, Evan McNeil, Kevin Bernard, Itzayana G. Miller, Grant B. Ellsworth, Carrie D. Johnston, Eli J. Finkelsztein, Paul Zumbo, Doron Betel, Friederike Dundar, Maggie C. Duncan, Hope R. Lapointe, Sarah Speckmaier, Nadia Moran-Garcia, Michelle Premazzi Papa, Samuel Nicholes, Carissa J. Stover, Rebecca M. Lynch, Marina Caskey, Christian Gaebler, Tae-Wook Chun, Alberto Bosque, Timothy J. Wilkin, Guinevere Q. Lee, Zabrina L. Brumme, R. Brad Jones
Summary: In a cohort of people with HIV, COVID mRNA vaccination leads to a temporary increase in a specific profile of HIV-specific T-cell responses and a corresponding decrease in residual HIV RNA, indicating productive immune engagement with infected cells.
NATURE COMMUNICATIONS
(2022)
Article
Biotechnology & Applied Microbiology
Preethi B. Balakrishnan, Carissa S. Holmberg, Debbie K. Ledezma, Alberto Bosque, Rohan Fernandes
Summary: This study investigates the use of nanoparticles as carriers to deliver drugs for the reactivation of latent HIV infection. The results show that polymeric-coated nanoparticles are more effective than free polymers in activating latent HIV and enhancing immune activation.
Article
Oncology
Ryan Urak, Brenna Gittins, Citradewi Soemardy, Nicole Grepo, Lior Goldberg, Madeleine Maker, Galina Shevchenko, Alicia Davis, Shirley Li, Tristan Scott, Kevin V. Morris, Stephen J. Forman, Xiuli Wang
Summary: In this study, the impact of different shRNA elements on the knockdown efficiency of target genes in CAR T cells was evaluated. The results emphasize the importance of considering multiple shRNAs and their orientation for effective knockdown. It was also shown that using a strong promoter and avoiding self-targeting can enhance CAR T cell functionality. These findings provide a framework for the rational design of CAR T cells with shRNA-mediated knockdown capabilities, which can improve the therapeutic efficacy of CAR T cell-based immunotherapy.
Review
Virology
J. Natalie Howard, Alberto Bosque
Summary: Despite advances in antiretroviral therapy, the latent reservoir of HIV-infected cells remains a major hurdle in finding a cure. IL-15 and N-803 have shown potential in reactivating latent HIV and enhancing immune effector function, which are crucial for reducing latent reservoirs.
Article
Medicine, Research & Experimental
Shane D. Falcinelli, Jackson J. Peterson, Anne-Marie W. Turner, David Irlbeck, Jenna Read, Samuel L. M. Raines, Katherine S. James, Cameron Sutton, Anthony Sanchez, Ann Emery, Gavin Sampey, Robert Ferris, Brigitte Allard, Simon Ghofrani, Jennifer L. Kirchherr, Caroline Baker, JoAnn D. Kuruc, Cynthia L. Gay, Lindsey I. James, Guoxin Wu, Paul Zuck, Inmaculada Rioja, Rebecca C. Furze, Rab K. Prinjha, Bonnie J. Howell, Ronald Swanstrom, Edward P. Browne, Brian D. Strahl, Richard M. Dunham, Nancie M. Archin, David M. Margolis
Summary: This study demonstrates the synergy in latent reservoir activation when using inhibitor of apoptosis protein (IAP) antagonists in combination with bromodomain and extraterminal domain protein inhibitors (BETi). It also highlights the importance of HIV transcriptional elongation and splicing as barriers to latent HIV protein expression, providing a rationale for further exploration of IAPi+BETi in animal models of HIV latency.
JOURNAL OF CLINICAL INVESTIGATION
(2022)